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Workpackage 33 Overview

Early host responses to Salmonella and Campylobacter


Salmonella and Campylobacter are two important zoonotic pathogens that cause gastro-enteritis in humans. Both pathogens are transmitted through contaminated food and water, and various risk factors for development of gastro-enteritis due to Salmonella and Campylobacter infection have been identified in epidemiological studies. Infectious diseases caused by Salmonella and Campylobacter are the result of the complex interaction between these bacteria and their host. The pathogenesis depends both on bacterial components, such as virulence factors, and on host components, such as immune mechanisms to eliminate the pathogen and resolve the clinical manifestations.

Traditionally human infectious disease studies have focused on investigating the pathogens themselves, whilst only a few advances have been made in understanding the host responses. One particular reason for this slower advancement is the complexity of the host genome and its responses. Over the past decade the genome sequences of human and other hosts (e.g. mice) have been unravelled and technical developments such as large-scale genetic profiling and transcription profiling using micro-arrays, have now opened up a whole range of possibilities to study the role of host factors in host–pathogen interaction. Detailed insight into pathogen factors, and highly sophisticated diagnostics and typing of these bacteria have shown that, although this knowledge has contributed to detection of pathogens and epidemiology, it is not sufficient for optimal infection control. A better insight into host factors involved in the elimination of these pathogens will allow a more complete understanding of the interaction between Salmonella and Campylobacter and the host and, eventually, may lead to improved strategies for controlling these zoonotic diseases.

Aims

Workpackage 33 involves six European partner institutes (RIVM, VLA, ISS, SVA, ID and SSI) and its major aim is to study host responses to Salmonella and Campylobacter infection using both novel techniques, i.e. microarray analysis and confocal microscopy, and more conventional immunologic techniques.

To study the role of host factors in determining disease susceptibility murine models of infection will be used. Comparing responses of highly susceptible mouse strains with relatively resistant mouse strains will enable the identification of early host responses that are associated with either development of severe disease or development of more moderate disease. Conversely, comparison of early host responses to pathogenic bacteria and bacterial mutants that are more or less virulent may shed light on whether and how the host can distinguish between strains with different virulence properties.

The final objective of this Workpackage is to evaluate whether this approach indeed increases our understanding of host–pathogen interaction and can lead to improved control of Salmonella and Campylobacter infection.


Riny Janssen
Enterocytes
Enterocytes

Progress


Workpackage 33 started in March 2007 and the first data have been collected:

  • standardized infection protocols have been agreed upon for Salmonella, and protocols for Campylobacter colonization are being set up;
  • characterization of early responses to Salmonella using microarray analysis shows that there is a clear difference in response between a highly susceptible strain of mice and a relatively resistant strain of mice;
  • analysis using confocal microscopy will be employed to identify processes that are activated upon infection;
  • to further distinguish responses in strains with different susceptibility to Salmonella infection, experiments in a second highly susceptible mouse strain have been initiated;
  • in parallel, early responses to Salmonella and Campylobacter are characterized using conventional immunological techniques.
 
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 Page Contact: Jennie Drew - Last modified: 2007-10-31